Phase III study on atezolizumab versus placebo in adjuvant therapy of pleural mesothelioma patients after pleurectomy/decortication: Preliminary results of the AtezoMeso study.

8087 Background: AtezoMeso Study is a multicentric double-blind, placebo-controlled, Phase III trial, that aims to evaluation the efficacy of adjuvant atezolizumab therapy versus placebo in patients with pleural mesothelioma (PM), who have undergone pleurectomy/decortication (P/D) and peri-operative chemotherapy. Here, we report preliminary data on disease recurrence and Next Generation Sequencing (NGS) testing. Methods: Patients with PM who have undergone P/D and perioperative platinum-pemetrexed chemotherapy are randomized 2:1 to receive atezolizumab or placebo for up to 12 months, or until unacceptable toxicity or patients’/physicians’ decision. The primary objective of the study is disease free survival (DFS), with a sample size of 90 patients. Surgical specimens are analyzed centrally to determine the genomic profile using FoundationOne CDx Platform. Results: Between December 2021 and January 2025, 64 patients were randomized in 14 Italian centers. The characteristics of patients included 46 (71.88%) males and 18 (28.12%) females. %), with a median age of 67 years (range 48-79). Sixty (93.75%) patients had epithelioid histotype, and 4 (6.25%) non-epithelioid. Sixteen (25%) patients are ongoing the adjuvant treatment. At the median follow up of 8.3 months (1-30 months), 25 (53.19%) of 47 evaluable patients experienced a disease recurrence. Sixteen (64%) of 25 patients had a local recurrence of disease, 5 (20%) patients an extra-thoracic recurrence, and 4 (16%) patients both. The median DFS of all evaluable patients was 12 months (7.4 - 16.6 months). The histotype of all relapsed patients was epithelioid. NGS testing was performed in 43 (67.19%) of 64 patients. Median Tumor Mutational Burden (TMB) was 2 mutations/megabase (0-13). The most frequent genomic alteration detected were BAP1 found in 21 (48.83%) patients, CDKNA2A-B in 18 (41.86%), NF2 in 8 (18.60%), SETD2 and TP53 in 5 (11.63 %). One (2.32%) patient had a mutation of BRCA2. The co-occurrence of BAP1 and CDKNA2A-B mutations was detected in 7 (16.27%) patients, all of whom had a disease recurrence. Conclusions: These preliminary dataof AtezoMeso Study, regarding all randomized patients, show a median DFS longer than expected in control arm according with the study design hypothesis (9 months). The TMB of MPM patients is low. BAP1 mutations were identified as the most frequent molecular alterations. Furthermore the co-occurrence of BAP1 and CDKNA2A-B mutations was found in patients with disease relapse. Clinical trial information: NCT04996017 .